OXYSTEROLS PRESENT IN ATHEROSCLEROTIC TISSUE DECREASE THE EXPRESSION OF LIPOPROTEIN-LIPASE MESSENGER-RNA IN HUMAN MONOCYTE-DERIVED MACROPHAGES

The presence of oxysterols in macrophages isolated from atheroscleroti c tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, fr eshly isolated from atherosclerotic aorta, show about the same distrib ution of oxysterols, analyzed by isotope dilution mass spectrometry, e xcept that all three preparations of human arterial-derived macrophage s contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL express ion, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxych olesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quan titative RT-PCR, Cholesterol and other tested oxysterols showed no eff ect on macrophage LPL mRNA expression compared with control. LPL activ ity in the medium was also reduced after exposure of the macrophages t o 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation wit h 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier obse rvation of a low level of LPL mRNA in arterial foam cells.